Modulation of morphine analgesia by site-specific N -methyl-d-aspartate receptor antagonists: dependence on sex, site of antagonism, morphine dose, and time

Nemmani, Kumar V.S.; Grisel, Judith E.; Stowe, Jennifer R.; Smith-Carliss, Richard; Mogil, Jeffrey S.

doi:10.1016/j.pain.2004.01.035

Cited by 70 publications

(55 citation statements)

References 56 publications

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“…The decrease in morphine analgesia found in the KO mice used in this study is consistent with others reports using pharmacological blockade of the NMDA receptor for morphine analgesia. For instance, dextromethorphan (a low affinity and non competitive antagonist) attenuates morphine analgesia at high dose, and the polyamine NR2B antagonist Ro 25-6981 attenuates morphine analgesia at all doses examined [27]. However, the present results also differ from other studies that evaluated the effect of NR2B receptor antagonism in morphine analgesia [3,9].…”

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confidence: 97%

“…Functionally, NMDA receptors are involved in coordinating motor responses [4,5,28], and are suggested to play a critical role in mediating pain and analgesia [29], including the analgesic effects of morphine [13,19,20,27]. …”

Section: Introductionmentioning

confidence: 99%

“…Those studies showed that antagonism of NR2B receptors increase the analgesic effects of morphine on phasic pain tests [3,9]. It can be appreciated that there is a high degree of variability in the effects of NMDA antagonists on morphine analgesia, as some studies have shown potentiation, whereas other studies attenuation or no effect [3,9,19,20,27,32]. Possible factors that could explain the lack of consistency in this kind of study include species, strain, opioid agonist used, dose, type of nociceptive stimulus, behavioral test, dose of NMDA antagonist, or interaction between factors [27].…”

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confidence: 99%

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Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1-subunit

Quintero

Erzurumlu

Vaccarino

2008

Neuroscience Letters

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Studies have shown that N-methyl-D-Aspartate (NMDA) receptors play a critical role in morphine analgesia and motoric processes at different levels of the central nervous system. In this study, we used cortex specific NR1 knockout mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in morphine analgesia and motor coordination. On post-natal day 20, mice (CTL and KO) received vehicle (saline) or morphine (10mg/kg) and paw withdrawal latency (PWL) to a noxious thermal stimulus was measured. On post-natal day 21, motor coordination was measured using the rotating pole test. No differences in KO mice were found with respect to PWL following administration of saline or morphine (p > 0.05). However, sex-dependent differences were in motor coordination, with male KO mice showing a greater motor impairment in the rotating pole test than female KO mice (p < 0.05). The present results demonstrate that NMDA receptors are involved in both the analgesic effects of morphine and motor coordination, with the existence of sex-related differences in motor coordination. KeywordsMotor coordination; morphine; analgesia; NMDA receptor; knockout; Noxious thermal stimuli N-methyl-D-Aspartate (NMDA) receptors are hetero-oligomers ligand-gated ion channel that interacts with diverse intracellular proteins [26], composed of subunits NR1, NR2 (A,B,C,D) and NR3 (A,B) [8,26]. Functionally, NMDA receptors are involved in coordinating motor responses [4,5,28], and are suggested to play a critical role in mediating pain and analgesia [29], including the analgesic effects of morphine [13,19,20,27].The present study was designed to elucidate further the role of NMDA receptors in mediating morphine analgesia and motor coordination by using NR1 -NMDA cortex-specific KO mice * Corresponding author at: Department of Psychology, University of New Orleans, New Orleans, Louisiana 70148, U.S. A., Tel: 504-280-1212; Fax: 504-280-6049., E-mail address: gaboquintero2006@yahoo.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KO [21] reported that these mice die at perinatal stage, being not possible to evaluate morphine analgesia and motor coordination aspects. NIH Public AccessWestern blot and in situ hybridization analysis reveals that, as compared with controls, NR1 -NMDA cortex-specific KO mice have a 95% reduction of NR1 subunit levels in cortex and hippocampus [12]. Using x-gal staining, the spatial restriction of Cre recombination has been verified at cortical levels [12]. Cortex-specific NR1 KO mice were originally generated by Iwasato et al. [12] by inserting the Cre recombin...

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confidence: 97%

Section: Introductionmentioning

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Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1-subunit

Quintero

Erzurumlu

Vaccarino

2008

Neuroscience Letters

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“…The distinction between the latter two types can be considered the difference between 'quantitative' and 'qualitative' sex differences. Although attention has mostly been paid to documenting quantitative sex differences in pain, a growing number of examples of qualitative differences in pain have been reported 31,39,43,[53][54][55][56][57][58][59][60][61][62][63][64] , and these promise to be far more important in the long run. As a practical matter, analgesics are routinely titrated according to their effect, which will effectively mitigate any sex differences along with other sources of inter-individual variability.…”

Section: Male Onlymentioning

confidence: 99%

“…Nature Reviews | Neuroscience qualitative sex differences in the midbrain, spinal cord and the primary afferent -are currently more comprehensively documented than the others. Multiple laboratories have observed that the midbrain-brain stem neural circuit subserving stress-induced analgesia, κ-opioid (and possibly μ-opioid) analgesia, morphine tolerance and morphine hyperalgesia in mice contains NMDAtype glutamate receptors (NMDARs) in males 49,56,57,[88][89][90] but not females; in many cases, females seem to use melanocortin 1 receptors (MC1Rs) instead 39,54,91 . In these studies, pharmacological antagonism with non-competitive NMDAR antagonists (for example, MK-801) blocks the phenomena in male but not female mice at any dose.…”

Section: Nature Reviews | Neurosciencementioning

confidence: 99%

Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon

2012

Self Cite

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| A clear majority of patients with chronic pain are women; however, it has been surprisingly difficult to determine whether this sex bias corresponds to actual sex differences in pain sensitivity. A survey of the currently available epidemiological and laboratory data indicates that the evidence for clinical and experimental sex differences in pain is overwhelming. Various explanations for this phenomenon have been given, ranging from experiential and sociocultural differences in pain experience between men and women to hormonally and genetically driven sex differences in brain neurochemistry. PERSPECTIVES NATURE REVIEWS | NEUROSCIENCE VOLUME 13 | DECEMBER 2012 | 859

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Animal models of chronic pain: Advances and challenges for clinical translation

Burma

Leduc‐Pessah

Fan

et al. 2016

J of Neuroscience Research

158

117

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Chronic pain is a global problem that has reached epidemic proportions. An estimated 20% of adults suffer from pain, and another 10% are diagnosed with chronic pain each year (Goldberg and McGee, ). Despite the high prevalence of chronic pain (an estimated 1.5 billion people are afflicted worldwide), much remains to be understood about the underlying causes of this condition, and there is an urgent requirement for better pain therapies. The discovery of novel targets and the development of better analgesics rely on an assortment of preclinical animal models; however, there are major challenges to translating discoveries made in animal models to realized pain therapies in humans. This review discusses common animal models used to recapitulate clinical chronic pain conditions (such as neuropathic, inflammatory, and visceral pain) and the methods for assessing the sensory and affective components of pain in animals. We also discuss the advantages and limitations of modeling chronic pain in animals as well as highlighting strategies for improving the predictive validity of preclinical pain studies. © 2016 Wiley Periodicals, Inc.

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Modulation of morphine analgesia by site-specific N -methyl-d-aspartate receptor antagonists: dependence on sex, site of antagonism, morphine dose, and time

Cited by 70 publications

References 56 publications

Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1-subunit

Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1-subunit

Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon

Animal models of chronic pain: Advances and challenges for clinical translation

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